Interobserver variability for the WHO classification of pulmonary carcinoids.

Pulmonary carcinoids are neuroendocrine tumors histopathologically subclassified into typical (TC; no necrosis, <2 mitoses per 2 mm) and atypical (AC; necrosis or 2 to 10 mitoses per 2 mm). The reproducibility of lung carcinoid classification, however, has not been extensively studied and may be hampered by the presence of pyknotic apoptosis mimicking mitotic figures. Furthermore, prediction of prognosis based on histopathology varies, especially for ACs.

Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome.

Carcinoids are slow-growing neuroendocrine tumors that, in the lung, can be subclassified as typical (TC) or atypical (AC). To identify genetic alterations that improve the prediction of prognosis, we investigated 34 carcinoid tumors of the lung (18 TCs, 15 ACs, and 1 unclassified) by using array comparative genomic hybridization (array CGH) on 3700 genomic bacterial artificial chromosome arrays (resolution ≤1 Mb). When comparing ACs with TCs, the data revealed: i) a significant difference in the average number of chromosome arms altered (9.

The clinical value of lymphatic micrometastases in patients with non-small cell lung cancer.

Introduction: In early stage non-small cell lung cancer (NSCLC), presence of lymphatic micrometastases and isolated tumor cells, primarily detected by immunohistochemistry, is suggested to be a prognostic factor. However, there is no consensus whether immunohistochemistry should be used routinely in lymph node assessment.The goal of our study was to determine whether recurrent disease is associated with the presence of lymphatic micrometastases and/or isolated tumor cells, at the time of the lung resection.

Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability.

Aims: To test the hypothesis that the published morphological criteria permit reliable segregation of small cell carcinoma of the lung (SCLC) and large cell neuroendocrine carcinoma (LCNEC) cases by determining the interobserver variation.

Methods And Results: One hundred and seventy cases of SCLC, LCNEC and cases diagnosed as neuroendocrine lung carcinoma before LCNEC had been established as a diagnostic category were retrieved from the archives of the assessor's institutes. A representative haematoxylin and eosin section from each case was selected for review.

Circulating DNA is a non-invasive prognostic factor for survival in non-small cell lung cancer.

Introduction: Circulating plasma DNA is present in a considerably higher concentration in lung cancer patients than in controls. Conflicting data are reported about circulating DNA as a prognostic factor. The aim of this study was to prospectively analyse the relationship of circulating plasma DNA with overall survival (OS) of previously untreated non-small cell lung cancer (NSCLC) patients.

Immunohistochemical markers associated with brain metastases in patients with nonsmall cell lung carcinoma.

Background: To the authors' knowledge, there are no reliable markers able to identify patients with nonsmall cell lung cancer (NSCLC) that will develop metastases to the brain. The authors investigated associations between immunohistochemical markers and the development of brain metastases in patients with NSCLC.

Methods: This was a hospital-based, case-control study of patients who were newly diagnosed with NSCLC between 1989 and 2003, developed brain metastases, and had pathology material available from both the primary NSCLC and the brain metastases.

Risk factors for non-sentinel lymph node metastases in patients with breast cancer. The outcome of a multi-institutional study.

Background: In this multi-institutional prospective study, we evaluated whether we could identify risk factors predictive for non-sentinel lymph node (non-SN) metastases in breast cancer patients with a positive sentinel lymph node (SN).

Methods: In this multi-institutional study, 541 eligible breast cancer patients were included prospectively.

Results: The occurrence of non-SN metastases was related to the size of the SN metastasis (P = .

A prospective study of the timing and cost-effectiveness of bronchial washing during bronchoscopy for pulmonary malignant tumors.

Study Objectives: The value of obtaining washings during fiberoptic bronchoscopy in the workup of lung cancer is controversial. Moreover, the optimal timing of washing relative to biopsy and brushing is not known. In this study, the diagnostic yields of washings before and after biopsy and brushings were compared.

Superoxide dismutase inactivation in pathophysiology of asthmatic airway remodeling and reactivity.

Airway hyperresponsiveness and remodeling are defining features of asthma. We hypothesized that impaired superoxide dismutase (SOD) antioxidant defense is a primary event in the pathophysiology of hyperresponsiveness and remodeling that induces apoptosis and shedding of airway epithelial cells. Mechanisms leading to apoptosis were studied in vivo and in vitro.

Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH), a fatal disease of unknown etiology characterized by impaired regulation of pulmonary hemodynamics and vascular growth, is associated with low levels of pulmonary nitric oxide (NO). Based upon its critical role in mediating vasodilation and cell growth, decrease of NO has been implicated in the pathogenesis of PAH. We evaluated mechanisms for low NO and pulmonary hypertension, including NO synthases (NOS) and factors regulating NOS activity, i.

Mitogen-activated protein kinase phosphatase-1 is overexpressed in non-small cell lung cancer and is an independent predictor of outcome in patients.

Purpose: An increase in the activity of the mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vitro and in vivo. A key regulatory mechanism of the MAPKs [extracellular signal-regulated kinase (ERK); c-jun NH(2)-terminal kinase (JNK); and p38] is the dual specificity phosphatase CL100, also called MAPK phosphatase-1 (MKP-1). This study was designed to examine the involvement of CL100/MKP-1 and stress-related MAPKs in lung cancer.

DNA microarray format for detection and subtyping of human papillomavirus.

A new human papillomavirus (HPV) assay using high-density DNA microarrays is described. An HPV DNA fragment from the 3' end of the E1 gene was amplified and digoxigenin labeled by PCR, and the resulting amplicons were hybridized onto type-specific oligonucleotides immobilized on high-density DNA microarrays. For detection, a simple immunohistochemical staining procedure was used with a substrate that has both colorimetric and fluorescent properties.

Diagnostic yield of transbronchial histology needle aspiration in patients with mediastinal lymph node enlargement.

Background: Transbronchial needle aspiration (TBNA) is a safe, minimally invasive technique to assess the mediastinal spread of lung cancer. Excellent results have been published by experts. However, little information is available about the diagnostic yield of TBNA with the histology needle in a non-expert center.

Microarray as a model for quantitative visualization chemistry.

For visualization of proteins or nucleic acids, direct and indirect in situ fluorescence and absorption methods (immunohistochemistry and cytochemistry) have existed for many years. The authors describe a new experimental approach using microarray as a model to quantitatively compare both visualization methods. The spots obtained with the microarray robot had a progressive twofold decrease in concentrations and are used as objects with known amounts of DNA.

Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis.

Purpose: Inflammation is a constant finding in the ileal reservoir of patients with an ileal pouch-anal anastomosis and is associated with decreased fecal concentrations of the short chain fatty acid butyrate, increased fecal pH, changes in fecal flora, and increased concentrations of secondary bile acids. In healthy subjects, inulin, a dietary fiber, is fermented to short chain fatty acids and leads to a lower pH and potentially beneficial changes in fecal flora. The aim of the present study was to investigate the effect of enteral supplementation of inulin on inflammation of the ileal reservoir.